Acrocallosal syndrome

Acrocallosal syndrome is a rare condition characterized by brain abnormalities, extra fingers or toes, and distinctive facial features.

Overview

Acrocallosal syndrome is present at birth, with severity varying widely among individuals. Key features include:

• Agenesis of the corpus callosum: The tissue connecting the left and right halves of the brain fails to form normally.
• Brain abnormalities: Large cysts may grow in brain tissue, leading to delayed development and moderate to severe intellectual disability. Some individuals experience seizures.
• Polydactyly: The presence of extra fingers and toes.
• Syndactyly: Webbed or fused skin between fingers or toes.
• Facial and head features: Widely spaced eyes (hypertelorism), a high forehead, and an unusually large head size (macrocephaly).

Causes

Mutations in the KIF7 gene cause acrocallosal syndrome. Mutations in the GLI3 gene can also cause features of this disorder; however, when caused by GLI3, it is sometimes considered a severe form of Greig cephalopolysyndactyly syndrome. Both genes are involved in the Sonic Hedgehog signaling pathway, which is critical for cell growth, specialization, and the patterning of the brain and limbs before birth.

Inheritance

• KIF7 mutations: Inherited in an autosomal recessive pattern, where both copies of the gene in each cell have mutations.
• GLI3 mutations: Considered autosomal dominant, where one copy of the altered gene is sufficient to cause the disorder. These cases often result from new (de novo) mutations occurring in reproductive cells or early embryonic development, with no family history of the disorder.